1,4-Dihydro-2,6-dimethyl-4-phenylpyridine-3,5-dicarboxylic acid diethyl ester is known to obtain by reacting 2-benzylideneacetoacetic acid ethyl ester, .beta.-aminocrotonic acid ethyl ester or acetoacetic acid ethyl ester and ammonia, as reported in Ber. Deutsch Chem. Ges. 31, 743(1971). DOS Nos. 2117517 and 2117573 disclose that similar compounds can be used as coronary arteriodilating and antihypertensive agents, and inter alia 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)pyridine-3,5-dicarboxylic acid dimethyl ester disclosed therein has been used extensively under the name of Nifedipine. Since commercial success of Nifedipine, a large number of compounds having similar chemical structure have been developed and these compounds are disclosed in U.S. Pat. Nos. 3,574,843; 4,264,611; 3,799,934; 4,239,893; 4,317,768; 4,044,141 and 4,258,042; EPO Appln. No. 0012180; and French Patent No. 2,182,983. Further, there are reported in No. WO 84/02132 the compounds wherein a heterocyclic group is linked to an alkylene group through an amide bond in an ester moiety at the 3-position of 1,4-dihydro-2,6-dimethyl-4-phenyl pyridine-3,5-dicarboxylic acid diesters. Known 1,4-dihydropyridine derivatives including Nifedipine inhibit calcium influx into the cells and they have been used as remedy for cardiac diseases of angina pectoris, etc., cerebrovascular diseases of cerebral infarction, etc., and hypertension.
However, it has been reported that these derivatives have the disadvantages such as short-lasting activity and tachycardia.
The present invention results from efforts to develop new compounds with more improved pharmacological effects and lesser side effects than known 1,4-dihydropyridine derivatives.